The effects of 5-fluorouracil and doxorubicin on expression of human immunodeficiency virus type 1 long terminal repeat

John Panozzo, Ender Akan, T. Daniel Griffiths, Gayle E. Woloschak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Previous work by many groups has documented induction of the human immunodeficiency virus (HIV) long terminal repeat (LTR) following exposure of cells to ultraviolet light and other DNA damaging agents. Our experiments set out to determine the relative activation or repression of the HIV-LTR in response to two classes of chemotherapeutic agents: Doxorubicin is a DNA damage-inducing agent, and 5-fluorouracil has an antimetabolic mode of action. Using HeLa cells stably transfected with a construct in which HIV-LTR drives expression of the chloramphenicol acetyl transferase reporter gene, we demonstrated an up to ten-fold induction following doxorubicin treatment at 24 h post-treatment. This induction was repressed by treatment with salicylic acid, suggesting a role for prostaglandin/cyclo-oxygenase pathways and/or NF-κB in the inductive response. Induction by 5-fluorouracil, in contrast, was more modest (two-fold at most) though it was consistently elevated over controls.

Original languageEnglish (US)
Pages (from-to)217-223
Number of pages7
JournalCancer Letters
Volume105
Issue number2
DOIs
StatePublished - Aug 2 1996

Keywords

  • 5-Fluorouracil
  • Chemotherapeutic agents
  • Doxorubicin/adriamycin
  • Human immunodeficiency virus (HIV) gene expression
  • Long terminal repeat of HIV

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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